Cancer therapy is a rapidly evolving field of medical research, with early detection, targeted therapies and personalised medicine improving survival outcomes globally across many cancer types.

However, the impacts of cancer do not stop after treatment. The disease is often a significant event in an individual’s lifetime and can have lasting physical and psychological effects which may be influenced by factors, such as age, lifestyle, the type of cancer or its treatment.

A new pilot study published in Biomedicines by researchers from the USA explores how patient age and the type of treatment given to cancer survivors could impact metabolic health, fatigue levels and their mental health.

Mitochondrial function and cancer therapies

Mitochondrial function is a key indicator of metabolic health. This critical cellular component is instrumental for cellular respiration to generate energy and maintain cellular homeostasis. It is also key to removing reactive oxygen species (ROS), a byproduct of cellular respiration, which can be harmful above normal levels.

An accumulation of ROS causes oxidative stress, eventually leading to DNA damage. Cancer treatments such as chemotherapy and radiotherapy disrupt the function of mitochondria present in both cancer cells and healthy cells to induce cell death. Hence, mitochondrial dysfunction leads to an accumulation of oxidative stress throughout the body.

Patients may experience symptoms such as fatigue, muscle weakness or cognitive decline when undergoing extensive pro-oxidant cancer therapies. These targeted treatments selectively kill cancer cells by increasing levels of reactive oxygen species. This, combined with age-related decline in energy reserves and cognition, can have lasting impacts on older patients who have undergone treatment and survived cancer.

“The published results explore how age and cancer treatment impacted energy mitochondrial function, skeletal muscle energetics, and psychosocial outcomes of cancer survivors. No one before this had looked deeply into single-cell-specific biology that can drive cancer patient experiences. There is some previous work on blood mitochondrial levels, but blood composition shifts constantly. Every time you sneeze, your blood cells differ.” – Prof. Leorey Saligan, senior author of the study.

Collecting patient-reported outcomes

This exploratory study used patient-related outcomes of eleven cancer survivors that underwent different types of cancer therapy, including chemotherapy, radiotherapy immunotherapy, hormonal therapy or combination therapy.

The following health components were measured as part of the study:

• Fatigue
• Physical function including handgrip strength
• Resilience
• Coping self-efficacy
• Phosphocreatine recovery time (tPCr) – a key indicator of mitochondrial function and muscle recovery assessed using magnetic resonance spectroscopy (MRS)

Alongside data obtained from patient-reported outcomes, the researchers included the Functional Assessment of Chronic Illness Therapy-Fatigue, to gauge how fatigue impacted quality of life and daily tasks. Other health assessments were carried out which evaluated mental health and patient quality of life.

To deepen the assessment of physical function, the researchers asked participants to carry out standardized physical tests, as well as instructing them to wear wearable activity trackers on the days following the MRS scan to track daily step counts.

Older cancer survivors demonstrate higher levels of fatigue

From the small sample of 11 participants, the results revealed that older participants demonstrated longer tPCr times, indicating weaker mitochondrial function, which was also reflected by slower muscle energy recovery, weaker grip strength and higher self-reported fatigue compared to younger patients. Resilience and self-efficacy were a little higher in older patients, but these scores were not statistically significant.

Surprisingly, however, longer tPCr times, was associated with reports of lower levels of fatigue in younger patients.

“It just shows that the subjective experience of fatigue is very multidimensional,” Saligan said. “It’s not only the physical aspect that’s dictating that symptom experience.”

Interestingly, patients who received multiple types of therapies exhibited higher levels of mitochondrial function but lower muscle strength and high levels of fatigue. Patients who underwent immunotherapy reported high levels of fatigue and lower physical activity, such as lower number of daily steps.

These seemingly counterintuitive results demonstrate the complexity of fatigue-related symptoms, recovery and mitochondrial function.

Small sample size calls for cautious interpretation

The authors emphasise the exploratory nature of the study and its small sample size, therefore the results require cautious interpretation.

Other limitations included tracking by consumer-grade wearable devices which may not accurately capture step counts and small movements, which are common among patients. Important aspects such as cancer stage and other diseases or health conditions were not considered in the present study.

Nonetheless, this preliminary study provides analysis of how age and treatment impact cellular energetics, physical function and fatigue symptoms from patient-reported outcomes.

“It is really important to see how soon exercise can really accelerate recovery of the muscles, but also utilization of the energy in the muscles,” Saligan said. “I think that is really critical for exercise dosing, but also timing exercise programs, for survivors.”

Future research with larger, more comprehensive cohorts is needed to understand the mechanisms of how age and cancer treatments impact mitochondrial function and psychosocial symptoms in cancer survivors.

To read more research about cancer biology, you can read articles published in Cancers or the journal Biomedicines in the section Cancer Biology and Oncology.